RESEARCH PROJECT 1: PROJECT SUMMARY Dysregulation of the hypothalamic-pituitary-adrenal axis has been suggested as a mechanism through which social and biological factors contribute to racial disparities in cancer outcomes. A prolonged and elevated glucocorticoid (GC) response following a social stressor predicts tumor growth rates and the development of rodent cancers that histologically and etiologically resembles human disease. The GC response is a key biomarker for allostatic load, which is a measure of biological responses to stressors. Many African Americans experience stressful life events and circumstances, including economic, discriminatory, and other stressors. These psychosocial factors may contribute to the well-documented poorer outcomes experienced by African American men with prostate cancer. However stress reactivity (SR), or one's physiological and psychological responses to a stressor, is highly individualized and dependent on psychological and social determinants as well as genetic factors. Investigators at MUSC will investigate the role of SR in the development of immune responses to prostate cancer among subjects participating in a prostate vaccine trial. The trial itself will be conducted to document the effects of a poxvirus vaccine (PROSTVAC) on the cancer growth and immune responses of patients immediately after radical prostatectomy. MUSC investigators will be able to study these subjects to determine the levels of stress and stressors and the feasibility of using validated psychologic methods to characterize these parameters in older men. The specific aims of this study are to: (1) conduct a Phase II clinical trial of PROSTVAC vaccine in subjects at high risk of relapse after radical prostatectomy for prostate cancer as a platform to evaluate the effects of SR on the development of an effective anti-tumor immune response; (2) measure stress reactivity among prostate cancer patients at risk for relapse based on socioeconomic status, glucocorticoid receptor (GR) polymorphisms, perceptions of social stressors, and allostatic load; and (3) compare the magnitude and distribution of stress responses with clinical and immunologic measures of vaccine effect. This clinical trial will provide a ?real world? setting of immunotherapy and immune response development in prostate cancer patients as they are experiencing an acute cancer- related stressor (e.g., risk for recurrence). In addition, this research will provide novel empirical data on the frequency and kinds of stress in prostate cancer survivors, their physiological responses to a validated laboratory stressor, and the associations between SR and clinical, genomic, and immunologic parameters important in immunotherapy.